Articles: brain-injuries.
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Laboratory studies have identified numerous potential therapeutic interventions that might have clinical application for the treatment of human traumatic brain injury. Many of these therapies have progressed into human clinical trials in severe traumatic brain injury. Numerous trials have been completed, and many others have been prematurely terminated or are currently in various phases of testing. ⋯ In this review, we summarize the current status of human traumatic brain injury clinical trials, as well as the animal laboratory studies that led to some of these trials. We summarize criteria for conducting clinical trials in severe traumatic brain injury, with suggestions for future improvements. We also attempt to identify factors that might contribute to the discrepancies between animal and human trials, and we propose recommendations that could help investigators avoid certain pitfalls in future clinical trials in traumatic brain injury.
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Neurologic and neuropsychologic sequelae of crush head injury, which is produced by static forces occurring when the head is stationary and pinned against a rigid structure, were studied prospectively in a series of eight children ranging in age from 13 to 32 months. Hospital course, computed tomographic findings, and neurologic and developmental outcomes were examined. All children sustained pronounced cerebral trauma characterized by multiple fractures throughout the calvaria, extra-axial hemorrhages, and parenchymal contusions. ⋯ One year after the injury, five of the six children reevaluated had a good recovery. Motor scores were significantly lower than cognitive scores at baseline and showed the greatest degree of improvement over time. Neuropsychologic outcome after brain injury produced by static loading of the head is more favorable than from traumatic brain injury associated with dynamic loading.
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J. Cereb. Blood Flow Metab. · Aug 1999
Reduction of cognitive and motor deficits after traumatic brain injury in mice deficient in poly(ADP-ribose) polymerase.
Poly(ADP-ribose) polymerase (PARP), or poly-(ADP-ribose) synthetase, is a nuclear enzyme that consumes NAD when activated by DNA damage. The role of PARP in the pathogenesis of traumatic brain injury (TBI) is unknown. Using a controlled cortical impact (CCI) model of TBI and mice deficient in PARP, the authors studied the effect of PARP on functional and histologic outcome after CCI using two protocols. ⋯ PARP -/- mice demonstrated improved motor and memory function after CC versus PARP +/+ mice (P < 0.05). However, contusion volume was not different between groups. The results suggest a detri mental effect of PARP on functional outcome after TBI.